Enantiomeric Variability of Distaminolyne A. Refinement of ECD and NMR Methods for Determining Optical Purity of 1-Amino-2-Alkanols.

A Norrie Pearce,Tadeusz F Molinski,Brent R Copp

doi:10.3390/molecules24010090

A Norrie Pearce, Tadeusz F Molinski + Show 1 more

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https://doi.org/10.3390/molecules24010090

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Abstract

Sample configurations of distaminolyne A (1a); isolated from the ascidians Pseudodistoma opacum and P. cereum, and collected at different sites in New Zealand, were investigated by two methods: Exciton coupled electronic circular dichroism (EC ECD) of the corresponding N,O-dibenzoyl derivative 1b; and chiral reagent derivatization of 1a with (S)- and (R)-α-methoxyphenylacetic acid (MPA), followed by 1H-NMR analysis. Configuration and optical purity of 1a (%ee) was found to vary depending on the geographic distribution of ascidian colonies. An improved method for preparing N,O-diarenoyl derivatives of 1a was optimized. The EC ECD method was found to be complementary to the MPA-NMR method at different ranges of %ee.

Highlights

The natural products sphingolipids—characterized by homologs and highly-modified analogs of the canonical C18 long-chain base, D-erythro-sphingosine—are rare among plants and microbes, but prevalent in the diverse realm of marine invertebrates [1]
AA configurations are heterogeneous: The relative configuration (RC) and absolute configuration (AC) of 2-AAs vary from species to species
Configuration assignment to AAs is deceptively simple, and confounded by weak specific rotations that have been misinterpreted in the past leading to erroneous assignments [4], or no assignment, which defer the problem to total synthesis [5,6]

Summary

Introduction

The natural products sphingolipids—characterized by homologs and highly-modified analogs of the canonical C18 long-chain base, D-erythro-sphingosine—are rare among plants and microbes, but prevalent in the diverse realm of marine invertebrates [1]. The most common variations are 2-amino-alkane-1,3-diols and their ∆4 -unsaturated derivatives, corresponding to 1 and. Other variations include long-chain aminoalkanols (AAs), including 1-amino-2-alkanols (1-AAs), 2-amino-3-alkanols (2-AAs), and compounds that may be related to the latter through divergent biosynthetic pathways (e.g., long-chain 2H-azirines [2]). Many AAs are biologically active; for example, the simple homolog spisulosine from the clam Spisula polynyma inhibits cell proliferation by disassembly of actin stress filaments [3]. Configuration assignment to AAs is deceptively simple, and confounded by weak specific rotations that have been misinterpreted in the past leading to erroneous assignments [4], or no assignment, which defer the problem to total synthesis [5,6]. A single chirogenic center in 1-AAs is responsible for [α]D with magnitudes within a narrow range of ~±1–3; for example, in S-distaminolyne A (1a, [α]D −1), a C17 AA from the New

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